Cerebral oedema (CO) is a rare life-threatening complication of diabetic ketoacidosis (DKA) in children. We analysed the biochemical and therapeutic risk factors for CO in DKA by a retrospective review of 256 children hospitalized for DKA between February 2003 and March 2015. The demographic characteristics, biochemical variables and therapeutic interventions were compared between the patients with and without CO. CO was observed in 22 (8.6%) of the 256 subjects included in the study. One of these patients (5%) had a fatal outcome and two patients (9%) survived with neurological consequences. CO was significantly associated with severe DKA: lower initial venous pH (p < 0.001) and bicarbonate (p < 0.001), higher initial blood glucose (p < 0.01), urea level (p < 0.05) and baseline serum osmolality (р < 0.05). During the treatment of DKA, low serum phosphate level was found to be significantly associated with CO (p < 0.05). We also found significant dependence between the development of CO and the initiation of treatment for DKA in another facility before hospitalization in our hospital (p < 0.05), bicarbonate application (p < 0.001), higher fluid volume infused initially (p < 0.01) and delayed potassium substitution (p < 0.01). Severe ketoacidosis, hyperglycaemia and dehydration at presentation, and low serum phosphate during treatment are significantly related to CO formation in children with DKA. The initial severe acidosis and hyperglycaemia probably cause brain injury which progresses into CO in the course of developing hypophosphatemia and cerebral hypervolemia.

Background: Screening for presymptomatic type 1 diabetes (T1D) reduces the risk of diabetic ketoacidosis (DKA) and allows for early intervention with disease-modifying therapies. Despite the rising incidence of T1D in Bulgaria, screening initiatives remain limited. This pilot study aims to evaluate the feasibility of selective T1D screening in high-risk children and identify potential clinical associations with islet autoimmunity. Methods: The study targeted a recruitment of 250 children aged 0–18 years (200 with a relative with T1D and 50 without). Screening for islet autoantibodies (AABs), including glutamic acid decarboxylase (GADA), insulin (IAA), insulinoma-associated-2 (IA-2A), zinc transporter-8 (ZnT8A), and islet cell cytoplasmic autoantibodies (ICAs), was performed via chemiluminescence immunoassay (CLIA). Participants testing positive for one or more AABs were scheduled for longitudinal immunological and metabolic follow-up to evaluate the persistence of autoimmunity and disease progression. Results: Between October 2024 and February 2026, the pilot study recruited 210 participants (84% of the 250 target), including 160 children with a relative (target 200) and 50 without a family history of T1D (target 50). Within the high-risk group, seven children (4.4%) tested positive for a single autoantibody (3 GADA, 2 ZnT8A, 1 IA-2A, and 1 IAA), while no autoantibodies were detected in the group without a relative. No cases of multiple autoantibody positivity or stage 3 T1D were identified in either group. Furthermore, no statistically significant associations were observed between autoantibody positivity and secondary factors, including breastfeeding, allergic status, a high-glycemic diet, frequent illness, and personal history of autoimmune disease. Conclusions: The findings validate the feasibility of selective T1D screening in Bulgaria, driven by high public interest and successful recruitment across both high-risk and general population cohorts. While this exploratory study found no significant clinical correlations, it establishes a vital roadmap for larger, longitudinal research. Ultimately, this pilot framework provides a scalable model for implementing standardized early detection to reduce the burden of T1D on the national healthcare system.

Background: Type 1 Diabetes Mellitus (T1DM) arises from a fundamental breakdown of central immune tolerance within the thymus. Medullary thymic epithelial cells (mTECs) express the Autoimmune Regulator (AIRE) protein, which drives the promiscuous transcription of peripheral tissue-restricted antigens — including insulin — thereby creating a “genetic mirror” essential for the clonal deletion of autoreactive T-cells. Genetic susceptibility loci that reduce intrathymic insulin expression allow high-affinity insulin-reactive T-cells to escape negative selection and enter the periphery, where they ultimately orchestrate the progressive destruction of pancreatic β-cells. Despite decades of research, no therapeutic strategy has yet succeeded in restoring this upstream tolerogenic defect at its source. Hypothesis: I hypothesise that the thymic microenvironment can be bioelectronically reprogrammed to re-establish central immune tolerance in T1DM. Specifically, I propose that non-invasive application of 448 kHz radiofrequency (RF) fields, delivered via a wearable smart patch using subthermal Capacitive-Resistive Electric Transfer (CRET), can selectively upregulate AIRE -dependent insulin expression in mTECs, thereby restoring the intrathymic “immunological shadow” of the pancreatic β-cell. Proposed mechanism: The 448 kHz RF field is hypothesised to interact with L-type voltage-gated calcium channels (Cav1.2/Cav1.3) on mTEC membranes, inducing a controlled, subthermal Ca² ⁺ influx. This calcium signal is proposed to activate two parallel intracellular cascades: the MAPK/ERK pathway and the calcineurin/NFAT–NF-κB axis, both of which converge on transcriptional upregulation of AIRE and, consequently, enhanced intrathymic insulin ( Ins2 ) expression. Strengthened negative selection and the preferential generation of epigenetically stable Helios ⁺ Foxp3 ⁺ thymus-derived regulatory T-cells (tTregs) are predicted as downstream immunological outcomes. The hypothesis is testable and falsifiable through a structured programme of preclinical experiments in the Non-Obese Diabetic (NOD) mouse model, incorporating pharmacological pathway dissection, live-cell calcium imaging and longitudinal immune phenotyping. Significance: This approach represents a conceptual shift from peripheral immunosuppression or symptomatic glycaemic management towards upstream, disease-modifying bioelectronic intervention. By targeting the embryologically conserved thymic–pancreatic axis, the 448 kHz CRET strategy offers a non-invasive, paediatric-compatible platform to arrest the autoimmune cascade at its immunological origin, with potential implications for the prevention and early interception of T1DM.

Introduction and aim. Floating-Harbor syndrome (FHS) is a very rare disease, whose typical characteristics include short stature, facial dysmorphic features and significant speech delay. We aim to present the first reported case of FHS with discordant growth hormone tests and confirmed hypoplasia of the pituitary gland. Description of the case. We report a case of a boy aged 8 years and 3 months with a height constantly below the 3rd percentile, delayed bone age in comparison to chronological age, typical dysmorphic triangular face and a high-pitched voice. Whole-exome sequencing (WES) detected a heterozygous pathogenic variant in SRCAP gene – a confirmation of the diagnosis Floating-Harbor syndrome (FHS). Recombinant human growth hormone (rhGH) therapy at a dose of 0.033 mg/kg/day (0.65 mg/day) was initiated at the age of 7 years and 10 months. Because of the insufficient growth velocity at the time of manuscript preparation a dose increase was made to 0.035 mg/kg/day (0.80 mg/day). Conclusion. In children presenting with short stature (especially when GH deficiency is confirmed), facial dysmorphism and developmental delay, Floating-Harbor syndrome should be considered as a possible diagnosis. A multidisciplinary approach involving pediatric endocrinologists, geneticists and developmental specialists is essential for timely etiological diagnosis and optimal management.

Background: Type 1 diabetes (T1D) incidence is rising at 3–5% per year. Autoantibody (AAB) screening identifies at-risk children pre-symptomatically, yet the clinical significance of single AAB positivity and its short-term trajectory remain incompletely characterized. Methods: Five T1D-associated AABs (anti-GAD65, anti-IA2, anti-ZnT8, ICA, IAA) were measured in 210 Bulgarian children (160 with first-degree T1D relatives, 50 controls). Seven single-AAB-positive children received lifestyle counseling (low-glycemic-index diet, physical activity ≥ 60 min/day) and were reassessed at 3 or 6 months with repeat AAB panels, HbA_1c, blood glucose and C-peptide. Results: Anti-GAD65 was the most frequent single AAB (n = 3), followed by anti-ZnT8 (n = 2), anti-IA2 (n = 1) and IAA (n = 1). None developed a second AAB or metabolic abnormalities. Titer dynamics were heterogeneous: two children showed apparent seroreversion (in one, substantially confounded by concurrent immunosuppressive therapy for an unrelated condition), one showed a ~15-fold titer reduction while remaining seropositive, one showed a minimal titer decrease, and three displayed mildly increasing titers. None progressed to multiple autoantibody positivity, and all maintained normal metabolic profiles. Conclusions: Favorable short-term outcomes were observed during follow-up of children with single autoantibody positivity. These findings suggest that single AAB positivity may follow a non-progressive course in some children. However, this study design cannot distinguish the contribution of lifestyle counseling from natural variability. Prospective controlled studies with larger cohorts, HLA stratification and longer follow-up are needed to determine whether lifestyle interventions can independently alter autoantibody dynamics and delay T1D progression.